New research identifies blood proteins signaling ALS up to ten years early.
A new study suggests that amyotrophic lateral sclerosis, better known as ALS or Lou Gehrig’s disease, might be detected many years before symptoms begin. Researchers have identified changes in blood proteins that could signal the disease up to a decade before muscle weakness or other problems appear. If confirmed, these findings could open the door to earlier diagnosis and better treatment strategies for a condition that has long been difficult to catch in its earliest stages.
ALS is a rare but devastating disorder that attacks nerve cells in the brain and spinal cord. Over time, it strips people of the ability to walk, talk, and even breathe on their own. The disease gained widespread public attention in 2014 through the Ice Bucket Challenge, a viral campaign that raised both money and awareness. While progress has been made in understanding the condition, one of the biggest obstacles has been the absence of a reliable early test. Most patients spend six months to a year and a half going through evaluations before receiving a diagnosis, and by that point, the disease is already advancing quickly. On average, survival after the first signs appear is just two to four years.
To tackle this problem, researchers at the National Institutes of Health studied nearly 3,000 plasma proteins, the building blocks and messengers in the blood that reflect activity in tissues and organs. They found 33 proteins that were consistently different in patients with ALS compared to those without the disease. This panel of proteins could act as a biomarker, essentially a signal in the blood that points to ALS before symptoms appear.
What made the findings striking was that some of these protein changes were linked to processes in skeletal muscle, nerve function, and energy metabolism as far as 10 years before the first outward signs. That kind of lead time could give doctors and patients a chance to act much earlier than is possible today.
The study also looked at patients with a specific genetic risk factor, the C9orf72 expansion, which is the most common inherited cause of ALS in people of European descent. In this group, the researchers noted eight proteins that were especially elevated, including markers tied to cellular stress and metabolism. These could serve as warning signs for those carrying the genetic variant.
To test whether the protein findings could be applied in practice, the team turned to machine learning. They compared different computer models and found that a method called random forest performed the best. This approach combined protein markers with factors such as age and sex to produce an “ALS risk score.” In trials, the model was highly accurate, reaching a performance level of more than 96 percent in identifying ALS cases. When tested on a much larger group of over 23,000 individuals, the accuracy climbed above 99 percent, showing that the system could reliably separate ALS from other neurological or muscular conditions.
Perhaps even more important, the risk score appeared to predict when symptoms would develop, before symptoms actually appear. The researchers reported that protein shifts were evident years before patients noticed weakness or other difficulties. This means the body may be making adjustments long before the disease becomes visible, offering an opportunity to intervene while there is still time to slow or change the course of illness.
The team acknowledged that their platform did not capture all possible proteins, and future studies will use broader methods and longer follow-up periods. Even so, the findings point to a real possibility that ALS could move from being diagnosed late to being recognized early.
The implications stretch beyond ALS. In the United Kingdom, a government-backed program is rolling out whole genome sequencing for every newborn, creating a digital health record that could track risks for rare conditions across a lifetime. For babies born with gene variants linked to diseases such as ALS, having blood protein markers as an added layer of screening could give doctors a clearer picture of future risk.
Together, advances in genome sequencing and protein analysis are reshaping how rare diseases are studied and detected. For ALS in particular, the discovery of early biomarkers marks a shift from waiting for decline to planning ahead for intervention. While no cure currently exists, the chance to act years earlier may change the outlook for patients and families facing one of the most devastating neurological conditions.
Sources:
Study points toward earlier and more accurate detection of ALS
A plasma proteomics-based candidate biomarker panel predictive of amyotrophic lateral sclerosis
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